The Comprehensive Sickle Cell Center (CSCC) at the Children's Hospital of Philadelphia is in its 14th year of operations. Our major goal has been to seek new information about the disease while translating acquired knowledge to the full benefit of the patient. In this regard, our CSCC has been organized from its inception with the care of the patients as its central focus around which research is organized. For the first time in the history of research in this genetic disease, a drug, hydroxyurea, has been licensed specifically for preventive management. Today, an increasing number of adult SCD patients lead lives of less pain and hospitalization because of their use of hydroxyurea. Bone marrow transplantation has succeeded in providing hematologic cure for 80% of those receiving sibling-matched donor transplant but this therapy is available for less than 15% of those who deserve a trial of it. Non-myeloablative transplant protocols now in early development promise to decrease post-transplant morbidity and increase the acceptability of stem cell transplantation to clinicians and patients/families. Transfusion therapy remains one of the most important therapeutic maneuvers in the management of SCD. Well-managed chronic transfusion therapy is able to keep an increasing number of patients from the occurrence or recurrence of major complications such as stroke, acute chest syndrome, and debilitating pain. In summary, progress has been made however, until we can assure the parents of a newborn with SCD that we can provide therapy that will prevent all the major and common complications of the disease, our work is far from being completed. This Center is excited about the opportunity to participate in the inter-Center collaborative clinical research studies, a new feature of the Comprehensive Centers for which we propose a prophylactic transfusion study. We have proposed a balanced program of exciting and innovative basic science research, a very promising translational project, and clinical and psychosocial studies that may lead soon to improved well-being of children and adolescents with sickle cell disease. We plan to continue our commitment to extend benefits of research to less developed areas of the sickle cell world.